Abstract Funds are requested to upgrade high-throughput genomic sequencing capabilities of the Genomics Core at the University of Kansas Medical Center through the purchase of an Illumina HiSeq 4000 sequencer. The Genomics Core (GC) has provided microarray services since 2002 and high throughput sequencing using the Illumina HiSeq 2000/2500 platform since 2011. Demand for our sequencing services has grown continuously since their inception, and we now provide services to a broad user base at the University of Kansas, affiliated Kansas Institutions, and throughout the Central Midwest region. Recent advances in sequencing technology have dramatically improved high throughput sequencing by reducing user cost, decreasing run time, and increasing the amount and quality of data; unfortunately, our current instrument is not able to take advantage of these key advances, with the result that the cost and quality of discovery by our investigators will suffer. The proposed upgrade to the Illumina HiSeq 4000 will ensure that our sequencing capabilities are and will remain optimal for the foreseeable future. The enhanced attributes of the HiSeq 4000 will be critical to supporting NIH-funded center grants that rely heavily on the Genomics Core, which include KUMC's Cancer Center, Alzheimer's Disease Center, Intellectual and Developmental Disabilities Research Center, Polycystic Kidney Disease Research Center, CTSA, and 3 Centers of Biomedical Research Excellence. The HiSeq 4000 will serve 28 major and 8 minor University of Kansas users with 31 (27 R01-equivalent) NIH grants, representing a subset of a larger user base at 25 institutions across a 14-state region. The HiSeq 4000 will be located in space already optimized for Illumina operations and will be integrated into a core network that provides comprehensive administrative infrastructure including online tracking of requests, automated billing, and user-polling for quality assurance, as well as bioinformatics and technical support and newly expanded IT infrastructure. New users are recruited using a proven, collaborative pilot program mechanism, and the GC is backed by a strong institutional commitment to both the acquisition and operation of the instrument. The acquisition of the Illumina HiSeq 4000 will enhance the rate and quality of scientific discovery of our large and diverse user group, but will also reduce costs to the investigator by approximately 57% per gigabase, thereby providing significant investigator savings that can be applied toward other NIH-funded research activities.